Match!

Endothelial nitric oxide synthase polymorphisms affect the changes in blood pressure and nitric oxide bioavailability induced by propofol

Published on May 1, 2018in Nitric Oxide3.371
· DOI :10.1016/j.niox.2018.02.007
Gustavo H. Oliveira-Paula10
Estimated H-index: 10
(USP: University of São Paulo),
Riccardo Lacchini16
Estimated H-index: 16
(USP: University of São Paulo)
+ 5 AuthorsJose E. Tanus-Santos46
Estimated H-index: 46
(USP: University of São Paulo)
Sources
Abstract
Abstract Propofol anesthesia is usually accompanied by hypotension, which is at least in part related to enhanced endothelial nitric oxide synthase (NOS3)-derived NO bioavailability. We examined here whether NOS3 polymorphisms (rs2070744, 4b/4a VNTR, rs3918226 and rs1799983) and haplotypes affect the changes in blood pressure and NO bioavailability induced by propofol. Venous blood samples were collected from 168 patients at baseline and after 10 min of anesthesia with propofol 2 mg/kg administered intravenously by bolus injection. Genotypes were determined by polymerase chain reaction and haplotype frequencies were estimated. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. We found that CT + TT genotypes for the rs3918226 polymorphism, the ba + aa genotypes for the 4b/4a VNTR and the CTbT haplotype were associated with lower decreases in blood pressure and lower increases in nitrite levels after propofol anesthesia. On the other hand, the TCbT and CCbT haplotypes were associated with more intense decreases in blood pressure and higher increases in nitrite levels in response to propofol. Our results suggest that NOS3 polymorphisms and haplotypes influence the hypotensive responses to propofol, possibly by affecting NO bioavailability.
  • References (51)
  • Citations (2)
📖 Papers frequently viewed together
2 Citations
200516.60Blood
5 Authors (A. Kyle Mack, ..., Gregory J. Kato)
270 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References51
Newest
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Lucas C. Pinheiro (USP: University of São Paulo)H-Index: 12
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 7 authors...
Abstract Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hyper...
2 CitationsSource
#1Pritam Sinharoy (Stanford University)H-Index: 6
#2Ian N. BratzH-Index: 19
Last. Derek S. Damron (KSU: Kent State University)H-Index: 11
view all 6 authors...
Background Transient receptor potential (TRP) ion channels have emerged as key components contributing to vasoreactivity. Propofol, an anesthetic is associated with adverse side effects including hypotension and acute pain upon infusion. Our objective was to determine the extent to which TRPA1 and/or TRPV1 ion channels are involved in mediating propofol-induced vasorelaxation of mouse coronary arterioles in vitro and elucidate the potential cellular signal transduction pathway by which this occu...
4 CitationsSource
#1Qi Zhong (HUST: Huazhong University of Science and Technology)H-Index: 1
#2Xiangdong Chen (HUST: Huazhong University of Science and Technology)H-Index: 1
Last. Shanglong Yao (HUST: Huazhong University of Science and Technology)H-Index: 16
view all 5 authors...
Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol w...
3 CitationsSource
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Marcelo R. Luizon (USP: University of São Paulo)H-Index: 14
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 7 authors...
Protein kinase C (PKC) signaling is critically involved in the control of blood pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with thel responses to ACEi. We examined whether PRKCA (Protein Kinase C, Alpha) polymorphisms (rs887797 C>T, rs1010544 T>C, and rs16960228 G>A), or haplotypes, and gene-gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with ena...
9 CitationsSource
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Riccardo Lacchini (USP: University of São Paulo)H-Index: 16
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 3 authors...
Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system. NOS3 is encoded by NOS3 gene, which displays a large number of genetic polymorphisms such as single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and in...
13 CitationsSource
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Riccardo Lacchini (State University of Campinas)H-Index: 16
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 7 authors...
The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug....
8 CitationsSource
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Riccardo Lacchini (USP: University of São Paulo)H-Index: 16
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 3 authors...
ABSTRACT Nitric oxide (NO) is an important vasodilator with a well-established role in cardiovascular homeostasis. While mediator is synthesized from L-arginine by neuronal, endothelial, and inducible nitric oxide synthases (NOS1, NOS3 and NOS2 respectively), NOS3 is the most important isoform for NO formation in the cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are regulated at transcriptional, posttranscriptional, and posttranslational levels. The NOS3 gene, whi...
26 CitationsSource
#1Yan WangH-Index: 2
#2Huixuan ZhouH-Index: 2
Last. Li WangH-Index: 4
view all 6 authors...
Abstract Protein kinase C (PKC) isoforms improve endothelial nitric oxide synthase activity and contractile Ca sensitivity in blood vessels. These actions may have opposite effects on propofol-induced vasodilation. This study examines the hypothesis that propofol induces relaxation by enhancing the PKC-mediated nitric oxide synthesis in endothelium and/or inhibiting the PKC-regulated Ca sensitivity in vascular smooth muscle (VSM). Propofol (1-100 μM) induced greater relaxation in endothelium-int...
11 CitationsSource
#1Pritam Sinharoy (KSU: Kent State University)H-Index: 6
#2Hongyu Zhang (Southwest General Health Center)H-Index: 3
Last. Derek S. Damron (KSU: Kent State University)H-Index: 11
view all 6 authors...
We previously demonstrated that the intravenous anesthetic, propofol, restores the sensitivity of transient receptor potential vanilloid channel subtype-1 (TRPV1) receptors via a protein kinase C epsilon (PKCe)-dependent and transient receptor potential ankyrin channel subtype-1 (TRPA1)-dependent pathway in sensory neurons. The extent to which the two pathways are directly linked or operating in parallel has not been determined. Using a molecular approach, our objectives of the current study wer...
6 CitationsSource
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Riccardo Lacchini (USP: University of São Paulo)H-Index: 16
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 6 authors...
Purpose Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that affects blood pressure by promoting vasodilation mediated by nitric oxide. Angiotensin-converting enzyme inhibitors (ACEi) up-regulate the VEGF expression; thus, genetic polymorphisms in the VEGFA gene could affect the antihypertensive responses to these drugs.
15 CitationsSource
Cited By2
Newest
#1Gustavo H. Oliveira-Paula (USP: University of São Paulo)H-Index: 10
#2Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
: Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. While enzymes with nitrite-reductase activity capable of generating NO from nitrite may contribute to antihypertensive effects of nitrite, another mechanism involving the generation ...
3 CitationsSource
#1Marcelo R. Luizon (UFMG: Universidade Federal de Minas Gerais)H-Index: 14
#2Daniela A. Pereira (UFMG: Universidade Federal de Minas Gerais)H-Index: 1
Last. Jose E. Tanus-Santos (USP: University of São Paulo)H-Index: 46
view all 3 authors...
: Endothelial nitric oxide synthase (NOS3) is a key enzyme responsible for nitric oxide (NO) generation in the vascular endothelium. Endothelial dysfunction is characterized by reduced NO production, and is a hallmark of cardiovascular diseases. Drugs with cardiovascular action may activate NOS3 and result in NO release and vasodilation. Moreover, genetic variations affect NOS3 expression and activity, and may partially explain the variability in the responses to cardiovascular drugs. We reviewe...
Source